Medicinal and Pharmaceutical Chemistry Commons^™

Phytochemical And In-Vitro Cytotoxic Analyses Of Flavonoid Species Isolated From Chromolaena Leivensis, Luke A. Bryant

Electronic Theses and Dissertations

As a leading cause of death worldwide, cancer and its treatments remain a primary source of interest among researchers. Modern studies are looking into bioselective cytotoxicity to create new chemotherapies that do not have the same harsh side effects as those we use today. Natural product research has a promising future for the development of such treatments. Specifically, polar flavonoids may be the key to a bioselective treatment. Such flavonoid species are native to plants, often within flower petals or within the body. A natural antioxidant, they are designed not to harm healthy cells. This study focuses on the plant …

Bioactive Constituents And Pharmacological Activities Of Curcuma Zedoaria: A Mini-Review, Abdulmutalib Allaq, Muneer M. Saleh Mohammed Saleh Alsayadi, Mustapha Salihu, Hasan M. Agha, Amena Hassan Hassan Gheeth, Fatimah Salim, Norrizah Jaafar Jaafar Sidik

AUIQ Complementary Biological System

Curcuma zedoaria Rosc. (white turmeric) is a rhizomatous medicinal plant in the Zingiberaceae family, widely used in traditional Asian medicine. In recent years, increasing scientific attention has focused on its diverse pharmacological properties and bioactive constituents. This mini review summarises current knowledge of the phytochemical composition and biological activities of C. zedoaria, with particular emphasis on its antimicrobial, antioxidant, anti-inflammatory, and anticancer effects. Phytochemical investigations using analytical techniques such as GC–MS and HPLC have revealed the presence of numerous bioactive compounds, including sesquiterpenes (example, germacrone, curzerenone, and curdione) and curcuminoids, which contribute to its therapeutic potential. Experimental studies demonstrate …

Protein Allostery Probed By Ligands Across Sites, Virgil A. Woods

Dissertations, Theses, and Capstone Projects

Allostery is a pervasive regulatory principle throughout biology, yet the structural pathways by which distal inputs alter active‑site chemistry within protein structures remain incompletely defined and exploited. This dissertation uses protein tyrosine phosphatase 1B (PTP1B) as a tractable model to map those pathways with complementary experimental and computational tools. I integrate high‑resolution hydrogen-deuterium exchange mass spectrometry (HDX-MS), room-temperature crystallography, NMR, steady-state kinetics, crystallographic pseudo-ensembles, and machine-learning-guided ligand discovery. The working premise is that regulation reflects redistribution within a conformational ensemble rather than a binary switch. That orthogonal perturbations by small molecules, mutations, and protein partners can be used to both …

Development Of Tunable Rose Bengal Based-Nanogumbos As Potential Selective Chemotherapeutic Agents, William J.A. Russell

Honors College Theses

As cancer remains one of the greatest threats to the global population, the development of chemotherapeutic agents that are selective and tunable is of critical importance. Herein, a series of Rose Bengal (RB)-based GUMBOS, a group of uniform materials based on organic salts, were synthesized via counterion exchange between [Na]₂[RB] and three organic cations: tetrabutylphosphonium bromide [TBP][Br], tetraphenylphosphonium chloride [TPP][Cl], and 1-dodecyl-3-methylimidazolium chloride [C₁₂MIm][Cl]. The resulting GUMBOS were characterized through FT-IR, ESI-MS, NMR, and UV-Vis Spectroscopy. Partition coefficient studies indicated all GUMBOS exhibited hydrophobic physiochemical characteristics. These hydrophobic RB-based GUMBOS …

Investigating The Role Of Traditional Chinese Herbal Medicine For Cancer Symptom Management In Older Adults: A Rapid Review, Isabelle C. Karshner

Honors Undergraduate Theses

Background: Patients with cancer often experience symptoms related to disease, complications, and treatment. One potential method of alleviating these symptoms is traditional Chinese herbal medications (TCHM). This rapid review explores the role of traditional Chinese herbal medications in treating cancer-related symptoms in older adults.

Purpose: The purpose of this rapid review is to gain and provide a better understanding of the effects of TCHM on cancer-symptom management in the older adult population. This review explores the association between TCHM and effects on cancer symptoms in older adults, including interactions, toxicity, and signs/symptoms of TCHM use that may be useful information …

Antituberculosis Potential Of Borrelidin Derivatives: An In Silico Molecular Docking And Molecular Dynamic Approach, Teni Ernawati, Donny Ramadhan, Faris Hermawan, Sasmito Wulyoadi, Bambang Marwoto, Ahmad Wibisana, Bambang Srijanto

The Thai Journal of Pharmaceutical Sciences

Background: The present tuberculosis (TB) treatment requires a significant time commitment, often lasting from 6 months to 2 years, with strict daily adherence. Non-compliance leads to drug resistance and suboptimal outcomes. Present research indicates that borrelidin shows potential activity against Mycobacterium tuberculosis, including strains that are resistant to first-line medications. Borrelidin has shown remarkable activity against M. tuberculosis H37Rv, with a minimum inhibitory concentration value of 3.12 μg/mL. Therefore, investigating the inhibition activity of borrelidin derivatives was essential for finding new anti-TB candidates. Objectives: This study aims to investigate the effects of 31 borrelidin derivative compounds …

Synthesis Of Tu100 Analogs And Biological Assays, Feyisope Tonye Oladapo

College of Graduate Studies: Theses & Dissertations

TU100 (14-methyl-5H-5,12-epiminobenzo[4,5]cyclohepta[1,2-b]naphthalene-6,11,13(12H)-trione) exhibits exceptional chemotherapeutic properties. It operates via a distinct mechanism that triggers cell death to create cytotoxic effects while concurrently inhibiting topoisomerase I and II. Its efficacy rivals that of well-known chemotherapeutic drugs like Daunorubicin. The distinctive characteristics of TU100 have led to initiatives aimed at creating structurally similar compounds to discover even more effective bioactive alternatives.

The analog synthesis incorporated quinoxaline or its derivatives (diphenyl quinoxaline, dipyridinyl quinoxaline, and dibenzophenazine-10,13-dione) that have been shown to have promising chemotherapeutic effects. Synthesizing the hetero naphthoquinones required a multi-step synthetic process, so quinoxaline/ derivatives intermediates are first prepared, then the …

Design, Synthesis, And Nmr-Guided Characterization Of A Targeted Covalent Inhibitor-Like Molecule Against Ivyp1 From P. Aeruginosa, Samuel Taylor Moore

Master's Theses

Multi-drug resistance poses a serious threat to future generations and historical antibiotic pipelines; consequently, the medical and economic burdens associated with treating multidrug-resistant bacteria are substantiated. In this context, P. aeruginosa (PA) emerges as one of the most significant healthcare challenges, being a leading cause of resistance-associated mortality worldwide. Despite modern efforts to combat these poor outcomes, drug-resistant cases continue to rise, and the need for novel antibiotic treatment is apparent. To this end, we investigated relevant resistance mechanisms and past antibiotic targets within PA, and in doing so, we identified relationships between peptidoglycan biology and a periplasmic protein, Inhibitor …

Synthesis Of Photocleavable Molecules For Neurological Applications, Nishal Madujith Egodawaththa Arachchilage Don

Theses and Dissertations

In recent biomedical research, the precise control of molecular dynamics through light activation has emerged as a powerful tool, particularly in the field of neurobiology. This approach involves the use of photocleavable cages or photoprotective groups (PPGs) that are chemically tethered to biologically active molecules such as neurotransmitters or calcium chelators. These cages remain inert until exposed to specific wavelengths of light, typically in the visible range, triggering the release of the active compound with high spatiotemporal precision.

For neurotransmitter systems, such as glutamate (Glu), which plays a critical role in synaptic transmission and memory formation, researchers have developed novel …

An Integrative Review Of The Absorption Of Fda-Approved Chemical Sunscreen Filters Into The Blood, Srinidhi Banala, Samrat Gollapudi, Abhiram Gollapudi, Bhaumik Patel

Rowan-Virtua Research Day

Introduction: This integrative review examines the absorption of FDA-approved chemical sunscreen filters, specifically avobenzone and oxybenzone, into the bloodstream. The study aims to compare the levels of absorption and potential health effects of systemic exposure to these sunscreen ingredients in the United States.

Methods: The researchers conducted a literature search of 57 articles, of which 15 were used for the review. Inclusion criteria focused on studies discussing absorption levels of avobenzone and oxybenzone, as well as methods of absorption into the bloodstream. Exclusion criteria included sunscreen ingredients not approved in the United States, non-English studies, and studies on methods to …

Design And Synthesis Of Small Molecule Drugs For Cns Disorders, Kirsten T. Tolentino

Theses & Dissertations

Dopamine (DA) is an important neurotransmitter for the regulation and long-term function of the central nervous system (CNS). DA binds to Dopamine Receptors (DR) to stimulate or inhibit adenyl cyclase production to further elicit a pharmacological response. DRs were cloned, and it was determined that there are two families separated by their function and five total subtypes distinguished by their amino acid structure. The Dopamine 4 receptor (D4R) is the second least studied subtype but has high expression in the frontal cortex, amygdala, hippocampus, hypothalamus, globus pallidus, substantia nigra pars reticula, and thalamus. Dopamine signaling and transmission, especially in the …

Various Synthetic Pathways Towards Efavirenz And Its Analogs; The Replacement Of The Side Chain, Elizabeth S. Bautista

Selected Honors Theses

Cyclopropyl acetylene (CA) is a key intermediate in the synthesis of the human immunodeficiency virus (HIV) reverse transcriptase inhibitor, Efavirenz (EFV), an antiviral drug used to treat HIV. CA is an expensive raw material, difficult to obtain, and employed in the preparation of medications to combat acquired immunodeficiency syndrome (AIDS). It was found that the structure could be synthesized by the utilization of PCl5; however, this resulted in unwanted ring opening products. To address this issue, a one pot synthesis was developed using Ph3PCl2 as a mild chlorinating agent. In addition, a new analog has been proposed substituting the cyclopropyl …

Development Of A Chemical Biology Approach To Uncover The Influence Of Sequence Variations On Ces1 Activity In Live Cells, Samuel James Knebel

Masters Theses

Drug metabolism is the biochemical process of modifying drugs to detoxify and remove them through enzymatic transformations. These biotransformation’s occur primarily in the liver and are critical to understanding how pharmaceutical compounds are chemically altered inside the human body. Human carboxylesterases (CESs) catalyze the hydrolysis of esters, amides, thioesters, and carbamates. CES-mediated hydrolysis plays an important role in the metabolism of many drugs including the first FDA approved antiviral treatment for COVID-19, remdesivir (Veklury), the seizure control medication rufinamide (Banzel), and the flu antiviral drug oseltamivir (Tamiflu). CES activity is known to be influenced by a variety of factors including …

Designing And Synthesizing A Warhead-Fragment Inhibitory Ligand For Ivyp1 Through Fragment-Based Drug Discovery, Samuel Moore

Symposium of Student Scholars

Fragment-based drug discovery (FBDD) is a powerful tool for developing anticancer and antimicrobial agents. Within this, magnetic resonance spectroscopy (NMR) provides a comprehensive qualitative and quantitative approach to screening and validating weak and robust binders with targeted proteins, making NMR among the most attractive strategies in FBDD. Inhibitor of vertebrate lysozyme (Ivyp1) of P. aeruginosa serves as an excellent target because of its active cellular location and implications in clinical prognosis for cystic fibrosis and immunocompromised patients. This study uses current NMR and biophysical techniques to develop a covalent, fragment-linked warhead inhibitor for Ivyp1 through synthetic methods, warhead linking, and …

Development Of Once-A-Year Injectable Formulation Of Cabotegravir For Prevention And Treatment Of Hiv Infection, Tanmay Abhay Kulkarni

Theses & Dissertations

Long-acting cabotegravir (CAB) extends antiretroviral drug (ARV) dosing to monthly for maintenance of human immunodeficiency virus type one (HIV-1) suppression and to every other month for prevention of viral transmission. However, injection dose volumes, site reactions, and clinical oversights that are required remain obstacles towards broad usage. To meet these needs, surfactant coated hydrophobic and lipophilic CAB prodrugs were created with controlled prodrug dissolution, hydrolysis and drug tissue penetration. To such ends, fatty acid ester CAB nanocrystal prodrugs with 14, 18, and 22 added carbon chains were synthesized then nanoformulated as NMCAB, NM2CAB, and NM3CAB. These nanocrystal formulations were tested …

Science-Based Regulation Of Pharmacological Substances In Competition Horses, Jacob Machin

Theses and Dissertations--Toxicology and Cancer Biology

Current testing methodologies within equine forensic toxicology focus on arbitrary thresholds and zero-tolerance policy. Modern analytical chemistry’s limits of detection are low enough that oftentimes femtogram-per-milliliter amounts of a substance can readily be identified in both blood and urine of a horse. For most pharmacologically relevant compounds, these concentrations have no relevance to pharmacological effect. It is therefore crucial that testing methodologies to determine appropriate thresholds and cut-offs be developed that are driven by biological activity rather than arbitrary limits of detection. This dissertation looks to address this by suggesting a system of calculated Effective Plasma Concentrations by which a …

Correlating The Physicochemical Properties Of Magnesium Stearate With Tablet Dissolution And Lubrication, Julie L. Calahan

Theses and Dissertations--Pharmacy

Magnesium stearate (MgSt) is the most commonly used pharmaceutical excipient and is present in over half the tablet formulations on the market. In spite of its popularity as an effective lubricant, it has been repeatedly recognized that there is significant variability between MgSt samples, which can cause inconsistent lubrication between batches of MgSt. The hypothesis of this research is that the batch-to-batch variability in tablet lubrication and dissolution observed in tablet formulations containing different MgSt samples can be correlated with differences in MgSt physicochemical properties (fatty acid salt composition, crystal hydrate form, particle size and surface area). Developing correlations between …

Synthesis And Characterization Of Long Acting Darunavir Prodrugs, Mary Banoub

Theses & Dissertations

Patient adherence is critical for ART success to ensure adequate viral suppression, therefore, long-acting antiretrovirals are soon replacing current daily regimens. In recent years, two drugs were successfully transformed into long-acting injectables; CAB LA and RPV LA. These long-acting nanoformulations made it possible to abandon the daily pill burden, instead approximately a bimonthly injection of both drugs is enough to suppress and maintain viral load suppression. Our laboratory has been instrumental in transforming FDA-approved and experimental-HIV medications into long-acting slow effective release drugs, also known as LASER ART. LASER ART consists of slow drug metabolism and high permeability and retention …

Iron-Containing Nanoparticles For The Treatment Of Chrionic Biofilm Infections In Cystic Fibrosis, Leisha M. A. Martin

Nanoscience and Microsystems ETDs

Cystic fibrosis (CF) is the most common genetic disease resulting in the morbidity and mortality of Caucasian children and adults worldwide. Due to a genetic mutation resulting in malfunction of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein, CF patients produce highly viscous mucus in their respiratory tract. This leads to impairment of the mucociliary clearance of inhaled microbes. In addition to reduced microbial clearance, anoxic environmental conditions in the lungs promote biofilm-mode growth of the pathogenic bacterial species Pseudomonas aeruginosa. Chronic infections of P. aeruginosa begin in early childhood and typically persist until respiratory failure and death result. The …

Structure-Activity Relationship Studies Of Synthetic Cathinones And Related Agents, Rachel A. Davies

Theses and Dissertations

Synthetic cathinones and related agents represent an international drug abuse problem, and at the same time an important class of clinically useful compounds. Structure-activity relationship studies are needed to elucidate molecular features underlying the pharmacology of these agents. Illicit methcathinone (i.e., MCAT), the prototype of the synthetic cathinone class, exists as a racemic mixture. Though the differences in potency and target selectivity between the positional and optical isomers of synthetic cathinones and related agents have been demonstrated to have important implications for abuse and therapeutic potential, the two MCAT isomers have never been directly compared at their molecular targets: the …

Design, Synthesis And Pharmacological Characterization Of Potential Mu Opioid Receptor Selective Ligands, Abhishek S. Kulkarni

Theses and Dissertations

Selective Mu Opioid Receptor (MOR) antagonists possess immense potential in the treatment of opioid abuse/addiction. Utilizing the “message-address” concept, our laboratory reported a novel, reversible, non-peptide MOR selective antagonist 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-[(4՛-pyridyl)carboxamido]morphinan (NAP). Molecular modeling studies revealed that the selectivity of NAP for the MOR is because of a π-π stacking interaction of its pyridine ring with the Trp318residue in theMOR. Pharmacological characterization showed that NAP is a P-glycoprotein substrate, thereby limiting its use in the treatment of opioid abuse/addiction. Thus, to modify NAP, we replaced the pyridine ring with its isosteric counterpart thiophene. Isosteric replacement …

A V-To-F Substitution In Sk2 Channels Causes Ca2+ Hypersensitivity And Improves Locomotion In A C. Elegans Als Model, Young-Woo Nam, Sabia N. Baskoylu, Dimitris Gazgalis, Razan Orfali, Meng Cui, Anne C. Hart, Miao Zhang

Pharmacy Faculty Articles and Research

Small-conductance Ca2+-activated K+ (SK) channels mediate medium afterhyperpolarization in the neurons and play a key role in the regulation of neuronal excitability. SK channels are potential drug targets for ataxia and Amyotrophic Lateral Sclerosis (ALS). SK channels are activated exclusively by the Ca2+-bound calmodulin. Previously, we identified an intrinsically disordered fragment that is essential for the mechanical coupling between Ca2+/calmodulin binding and channel opening. Here, we report that substitution of a valine to phenylalanine (V407F) in the intrinsically disordered fragment caused a ~6 fold increase in the Ca2+ sensitivity of SK2-a channels. This substitution resulted in a novel interaction between …

Site-Selective Modification Of Peptides And Proteins Via Organocatalyzed Henry Reaction, Zilma Pereira Muneeswaran

Seton Hall University Dissertations and Theses (ETDs)

In this research, peptides and protein containing serine on the N-terminus underwent site-selective modification following organocatalyzed bioconjugation that offered an additional functional group. It was shown that transforming the N-terminus serine to an aldehyde allowed site-specific bioconjugation to occur by utilizing the well-known Henry reaction. This method also grants a safer pathway for bioconjugation utilizing “green-chemistry” and biocompatible conditions. Amino acids and amino acid derived organocatalysts were utilized in the Henry reaction resulting in yields of up to 86 % conversion. Promising preliminary results were achieved in this research using peptides and myoglobin as the bioconjugation targets. Further investigation to …

Do Paraben Derivatives Alter T Cell Immunity?, Hailey Kintz

Spring Presentation of Undergraduate Research

T cells immunity is linked to a complex system of cytokines that determine differentiation of naïve T cells into Th1, Th2, Th17, and Treg cells. Estrogen production or periods of elevated production have been correlated with an anti-inflammatory state in which Th2 and Treg cells are up-regulated. Such responses in the immune system are capable of supporting pre-cancerous activity. We are investigating the tie between the xenoestrogen compounds found in cosmetics, parabens, and their ability to regulate T cell immunity. Testing parabens and paraben derivatives with weaker estrogen receptor association will allow for a better understanding of the interplay between …

Galantamine's Deconstruction In The Quest Of A Pam Pharmacophore, Malaika Argade

Theses and Dissertations

Alzheimer’s disease is a progressive neurodegenerative disorder generally affecting people above the age of 65 years. Even though the pathophysiological hallmarks of AD were established more than a hundred years ago, there is yet to be a drug that can stop its characteristic neuronal damage. Of the five currently FDA-approved drugs, galantamine has a unique mechanism of action. Apart from being an AChE inhibitor, galantamine can effectively potentiate (positive allosteric modulator) the effect of agonists at nAChRs at concentrations lower than those required for its action as an AChE inhibitor. Perhaps the clinical benefits observed with galantamine are associated mainly …

Difatty Acyl-Conjugated Linear And Cyclic Peptides For Sirna Delivery, Hung Do, Meenakshi Sharma, Naglaa Salem El-Sayed, Parvin Mahdipoor, Emira Bousoik, Keykavous Parang, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

A number of amphiphilic difatty acyl linear and cyclic R5K2 peptide conjugates were synthesized by solid-phase peptide methods to enhance the interaction with the hydrophobic cellular phospholipid bilayer and to improve siRNA delivery and silencing. Binding to siRNA molecules was significantly less for the cyclic peptide conjugates. A gradual decrease was observed in the particle size of the complexes with increasing peptide/siRNA ratio for most of the synthesized peptides, suggesting the complex formation. Most of the complexes showed a particle size of less than 200 nm, which is considered an appropriate size for in vitro siRNA delivery. A number of …

Substituent Strength Vs Reactivity: A Study Of 1,3,4-Oxadiazoles And Electron Donating Groups, Katlynn Merringer

Undergraduate Honors Thesis Projects

This investigation focused on determining if there was a relationship between electron donating group substituent strength and resulting percent yield values of the 1,3,4-oxadiazole product. The data obtained from this investigation aimed to help chemists better understand the reactivity of the 1,3,4-oxadiazole because of its importance in the realm of drug design and development. In order to accomplish this, electron donating groups with varying pKa values were placed on the 1,3,4-oxadiazole and the resulting percent yields were analyzed for possible trends. The substituents used represented both resonance donating and inductively donating groups and were placed in both ortho and para …

Synthesis Of Oxadeazoles With Electron Withdrawing Groups And The Analysis Of Product Yield With Bond Length, Elizabeth Ann Hall Peters

Undergraduate Honors Thesis Projects

2,5-disubstituted 1,3,4-oxadiazoles are a class of organic compound that are widely used and successful in pharmaceutical chemistry because they demonstrate strong biological activity. They are part of a larger class of compound called heterocycles, which make up most pharmaceutical drugs today. When synthesizing the compounds, higher yield means higher reactivity of the compound, and this is important for pharmaceuticals that need to have a strong biological activity. Per past studies, electron withdrawing groups on the compound allow higher, product yields. Along with electron withdrawing group addition, the bond length from electron withdrawing group and its corresponding carbon is analyzed to …

A Diversity-Oriented Synthesis Approach To Functionalized Azaheterocycles Using Cyclic Alpha-Halo Eneformamides, Spencer A. Langevin

All Master's Theses

Functionalized piperidines, azepanes, azamacrocycles, morpholines, and thiomorpholines are common structural motifs found in a wide range of pharmaceuticals such as carmegliptine, levofloxacin, thioridazine, claviciptic acid, and azithomycin. As a result, there is a strong desire to construct highly functionalized nitrogen-bearing ring scaffolds in order to construct a wide range of drug possibilities. There are several non-modular and step-uneconomical synthetic methods used in the construction of these aforementioned motifs such as ring closing metathesis, ring expansions, and intramolecular reductive amination. In this research, we present a step-economical, cost-effective, scalable, and diversity-oriented synthesis approach to highly functionalized N-heterocycles through the intermediacy of …

Chemoselective And Stereoselective Exploration Of The Chemical Reactivity Space Of Castagnoli-Cushman-Derived Allylic Lactamoyl Esters: Application To The Synthesis Of Aza-Polycyclic Architectures, Brandon Joseph Mansker

All Master's Theses

The synthesis and evaluation of structure-activity relationships of saturated nitrogen heterocycles is the focal point of various pharmaceutical companies thanks to the high biological activity of previously isolated azacycles. Here, we describe an operationally simple and highly efficient approach to macrocyclic lactams bearing vicinal stereocenters and a challenging cycloalkyne motif. The outcomes are achieved through a novel [4 + 2] cycloaddition reaction between an N-iodoarylated-1,3-azadiene and cyclic anhydrides, followed by interception of the cycloadducts in cross-coupling manifolds (e.g., Sonogashira coupling) and concomitant lithiation-cyclization of the tethered alkyne. An unprecedented example of a hydroamino alkylation that is transition …